Sympathetic tone dictates the impact of lipolysis on FABP4 secretion.
Sympathetic tone dictates the impact of lipolysis on FABP4 secretion.
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DOI：
10.1016/j.jlr.2023.100386
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发表时间：
2023-06
影响因子：
6.5
通讯作者：
Hotamisligil, Gokhan S.
中科院分区：
文献类型：
--
作者：
Prentice, Kacey J.;Lee, Alexandra;Cedillo, Paulina;Inouye, Karen E.;Ertunc, Meric Erikci;Riveros, Jillian K.;Lee, Grace Yankun;Hotamisligil, Gokhan S.
循环脂肪酸结合蛋白4（FABP 4）蛋白的水平与小鼠和人类中的肥胖和代谢性疾病密切相关，并且在体内和体外通过β-肾上腺素能刺激来刺激分泌。先前，发现脂解诱导的FABP 4分泌在脂肪甘油三酯脂肪酶（ATGL）的药理学抑制后显著降低，并且在脂肪细胞中特异性缺乏ATGL的小鼠的脂肪组织外植体中不存在（ATGLAdpKO）。在此，我们发现，在体内激活β-肾上腺素能受体后，与ATGLfl/fl对照相比，ATGLAdpKO小鼠出乎意料地表现出显著更高水平的循环FABP 4，尽管没有相应的脂解诱导。我们产生了脂肪细胞特异性缺失FABP 4和ATGL（ATGL/FABP 4AdpKO）的另外的模型，以评估这种循环FABP 4的细胞来源。在这些动物中，没有脂解诱导的FABP 4分泌的证据，表明ATGLAdpKO小鼠中FABP 4水平升高的来源确实来自脂肪细胞。ATGLAdpKO小鼠表现出显著升高的皮质酮水平，其与血浆FABP 4水平正相关。与对照组相比，在脂肪分解期间使用六甲铵或将小鼠置于热中性以长期降低交感神经张力的交感神经信号传导的药理学抑制显著降低了ATGLAdpKO小鼠中的FABP 4分泌。因此，由ATGL介导的脂解的关键酶促步骤的活性本身不是体内刺激脂肪细胞分泌FABP 4所必需的，其可以通过交感神经信号传导诱导。
Levels of circulating fatty acid binding protein 4 (FABP4) protein are strongly associated with obesity and metabolic disease in both mice and humans, and secretion is stimulated by β-adrenergic stimulation both in vivo and in vitro. Previously, lipolysis-induced FABP4 secretion was found to be significantly reduced upon pharmacological inhibition of adipose triglyceride lipase (ATGL) and was absent from adipose tissue explants from mice specifically lacking ATGL in their adipocytes (ATGLAdpKO). Here, we find that upon activation of β-adrenergic receptors in vivo, ATGLAdpKO mice unexpectedly exhibited significantly higher levels of circulating FABP4 as compared with ATGLfl/fl controls, despite no corresponding induction of lipolysis. We generated an additional model with adipocyte-specific deletion of both FABP4 and ATGL (ATGL/FABP4AdpKO) to evaluate the cellular source of this circulating FABP4. In these animals, there was no evidence of lipolysis-induced FABP4 secretion, indicating that the source of elevated FABP4 levels in ATGLAdpKO mice was indeed from the adipocytes. ATGLAdpKO mice exhibited significantly elevated corticosterone levels, which positively correlated with plasma FABP4 levels. Pharmacological inhibition of sympathetic signaling during lipolysis using hexamethonium or housing mice at thermoneutrality to chronically reduce sympathetic tone significantly reduced FABP4 secretion in ATGLAdpKO mice compared with controls. Therefore, activity of a key enzymatic step of lipolysis mediated by ATGL, per se, is not required for in vivo stimulation of FABP4 secretion from adipocytes, which can be induced through sympathetic signaling.
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影响因子：
82.9
作者：
Erbay, Ebru;Babaev, Vladimir R.;Mayers, Jared R.;Makowski, Liza;Charles, Khanichi N.;Snitow, Melinda E.;Fazio, Sergio;Wiest, Michelle M.;Watkins, Steven M.;Linton, MacRae F.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
DOI：
10.4137/cmc.s17067
发表时间：
2014
期刊：
Clinical Medicine Insights. Cardiology
影响因子：
--
作者：
Furuhashi M;Saitoh S;Shimamoto K;Miura T
通讯作者：
Miura T
影响因子：
9.8
作者：
Elmasri, Harun;Ghelfi, Elisa;Yu, Chen-wei;Traphagen, Samantha;Cernadas, Manuela;Cao, Haiming;Shi, Guo-Ping;Plutzky, Jorge;Sahin, Mustafa;Hotamisligil, Gokhan;Cataltepe, Sule
通讯作者：
Cataltepe, Sule
影响因子：
2.5
作者：
Cui X;Nguyen NL;Zarebidaki E;Cao Q;Li F;Zha L;Bartness T;Shi H;Xue B
通讯作者：
Xue B
影响因子：
5.3
作者：
DiPilato, Lisa M.;Ahmad, Faiyaz;Birnbaum, Morris J.
通讯作者：
Birnbaum, Morris J.